Completion total mesorectal excision after neoadjuvant radiochemotherapy and local excision for rectal cancer.

AIM: Local excision (LE) in selected cases after neoadjuvant radiochemotherapy (RCT) for locally advanced rectal cancer in clinically complete or major responders has been recently reported as an alternative to standard radical resection. Completion total mesorectal excision (cTME) is generally performed when high-risk pathological features are found in LE surgical specimens. The aim of this study was to evaluate the incidence of residual tumour and lymph node metastases after cTME in patients previously treated by RCT + LE. The secondary aims were to quantify the rate of postoperative morbidity and mortality and to evaluate the long-term oncological outcome of this group of patients. METHODS: All patients treated from 2007 to 2020 by LE for locally advanced rectal cancer with a clinically complete or major response to RCT who had a subsequent cTME for high-risk pathological factors (ypT >1 and/or TRG >2 and/or positive margins) were included in this multicentre retrospective study. Pathological data, postoperative short-term morbidity (classified according to Clavien-Dindo) and mortality and oncological long-term outcome after cTME were recorded in a database. Statistical analysis was performed using Wizard for iOS version 1.9.31. RESULTS: A total of 47 patients were included in the study. The rate of R0 resection was 95.7%, and a sphincter-saving procedure was performed in 37 patients (78.7%), with a protective stoma rate of 78.4%. In 28 cases (59.6%), it was possible to perform a minimally invasive approach. A residual tumour (pT and/or pN) on cTME specimens was found in 21 cases (44.7%). The rate of lymph node metastases was 12.8%. The overall short-term (within 30 days) postoperative morbidity was 34%, but grade >2 postoperative complications occurred in only nine patients (19.1%), with a reoperation rate of 6.4%. No short-term postoperative deaths occurred. At a median follow-up of 57 months (range: 21-174), the long-term stoma-free rate was 70.2%, and the actuarial 5-year overall survival (OS), disease-free survival (DFS) and local control (LC) were 86.7%, 88.9% and 95.7%, respectively. CONCLUSION: When patients exhibit high-risk pathological factors after RCT + LE, cTME should be suggested due to the high risk of residual tumour or lymph node involvement (44.7%). The results after cTME in terms of the rate of R0 resection, sphincter-saving procedure, postoperative morbidity and mortality and long-term oncological outcome seem to be acceptable and do not represent a contraindication to use LE as a first-step treatment in patients with major or complete clinical response after RCT.

Minimally invasive vs. open segmental resection of the splenic flexure for cancer: a nationwide study of the Italian Society of Surgical Oncology-Colorectal Cancer Network (SICO-CNN).

BACKGROUND: Evidence on the efficacy of minimally invasive (MI) segmental resection of splenic flexure cancer (SFC) is not available, mostly due to the rarity of this tumor. This study aimed to determine the survival outcomes of MI and open treatment, and to investigate whether MI is noninferior to open procedure regarding short-term outcomes. METHODS: This nationwide retrospective cohort study included all consecutive SFC segmental resections performed in 30 referral centers between 2006 and 2016. The primary endpoint assessing efficacy was the overall survival (OS). The secondary endpoints included cancer-specific mortality (CSM), recurrence rate (RR), short-term clinical outcomes (a composite of Clavien-Dindo > 2 complications and 30-day mortality), and pathological outcomes (a composite of lymph nodes removed ≧12, and proximal and distal free resection margins length ≧ 5 cm). For these composites, a 6% noninferiority margin was chosen based on clinical relevance estimate. RESULTS: A total of 606 patients underwent either an open (208, 34.3%) or a MI (398, 65.7%) SFC segmental resection. At univariable analysis, OS and CSM were improved in the MI group (log-rank test p = 0.004 and Gray's tests p = 0.004, respectively), while recurrences were comparable (Gray's tests p = 0.434). Cox multivariable analysis did not support that OS and CSM were better in the MI group (p = 0.109 and p = 0.163, respectively). Successful pathological outcome, observed in 53.2% of open and 58.3% of MI resections, supported noninferiority (difference 5.1%; 1-sided 95%CI - 4.7% to ∞). Successful short-term clinical outcome was documented in 93.3% of Open and 93.0% of MI procedures, and supported noninferiority as well (difference - 0.3%; 1-sided 95%CI - 5.0% to ∞). CONCLUSIONS: Among patients with SFC, the minimally invasive approach met the criterion for noninferiority for postoperative complications and pathological outcomes, and was found to provide results of OS, CSM, and RR comparable to those of open resection.

Rectal Sparing Approach After Neoadjuvant Therapy in Patients with Rectal Cancer: The Preliminary Results of the ReSARCh Trial.

BACKGROUND: Rectum-preservation for locally advanced rectal cancer has been proposed as an alternative to total mesorectal excision (TME) in patients with major (mCR) or complete clinical response (cCR) after neoadjuvant therapy. The purpose of this study was to report on the short-term outcomes of ReSARCh (Rectal Sparing Approach after preoperative Radio- and/or Chemotherapy) trial, which is a prospective, multicenter, observational trial that investigated the role of transanal local excision (LE) and watch-and-wait (WW) as integrated approaches after neoadjuvant therapy for rectal cancer. METHODS: Patients with mid-low rectal cancer who achieved mCR or cCR after neoadjuvant therapy and were fit for major surgery were enrolled. Clinical response was evaluated at 8 and 12 weeks after completion of chemoradiotherapy. Treatment approach, incidence, and reasons for subsequent TME were recorded. RESULTS: From 2016 to 2019, 160 patients were enrolled; mCR or cCR at 12 weeks was achieved in 64 and 96 of patients, respectively. Overall, 98 patients were managed with LE and 62 with WW. In the LE group, Clavien-Dindo 3+ complications occurred in three patients. The rate of cCR increased from 8- to 12-week restaging. Thirty-three (94.3%) of 35 patients with cCR had ypT0-1 tumor. At a median 24 months follow-up, a tumor regrowth was found in 15 (24.2%) patients undergoing WW. CONCLUSIONS: LE for patients achieving cCR or mCR is safe. A 12-week interval from chemoradiotherapy completion to LE is correlated with an increased cCR rate. The risk of ypT > is reduced when LE is performed after cCR.

THUNDER 2: THeragnostic Utilities for Neoplastic DisEases of the Rectum by MRI guided radiotherapy.

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) is the standard treatment modality in locally advanced rectal cancer (LARC). Since response to radiotherapy (RT) is dose dependent in rectal cancer, dose escalation may lead to higher complete response rates. The possibility to predict patients who will achieve complete response (CR) is fundamental. Recently, an early tumour regression index (ERI) was introduced to predict pathological CR (pCR) after nCRT in LARC patients. The primary endpoints will be the increase of CR rate and the evaluation of feasibility of delta radiomics-based predictive MRI guided Radiotherapy (MRgRT) model. METHODS: Patients affected by LARC cT2-3, N0-2 or cT4 for anal sphincter involvement N0-2a, M0 without high risk features will be enrolled in the trial. Neoadjuvant CRT will be administered using MRgRT. The initial RT treatment will consist in delivering 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum and 45 Gy in 25 fractions on the drainage nodes. Chemotherapy with 5-fluoracil (5-FU) or oral capecitabine will be administered continuously. A 0.35 Tesla MRI will be acquired at simulation and every day during MRgRT. At fraction 10, ERI will be calculated: if ERI will be inferior than 13.1, the patient will continue the original treatment; if ERI will be higher than 13.1 the treatment plan will be reoptimized, intensifying the dose to the residual tumor at the 11th fraction to reach 60.1 Gy. At the end of nCRT instrumental examinations are to be performed in order to restage patients. In case of stable disease or progression, the patient will undergo surgery. In case of major or complete clinical response, conservative approaches may be chosen. Patients will be followed up to evaluate toxicity and quality of life. The number of cases to be enrolled will be 63: all the patients will be treated at Fondazione Policlinico Universitario A. Gemelli IRCCS in Rome. DISCUSSION: This clinical trial investigates the impact of RT dose escalation in poor responder LARC patients identified using ERI, with the aim of increasing the probability of CR and consequently an organ preservation benefit in this group of patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04815694 (25/03/2021).

Transanal Endoscopic Microsurgery Versus Total Mesorectal Excision in ypT0-1 Rectal Cancer After Preoperative Radiochemotherapy: Postoperative Morbidity, Functional Results, and Long-term Oncologic Outcome.

BACKGROUND: In patients with locally advanced extraperitoneal rectal cancer, a multidisciplinary approach represents the standard treatment. However, considering the favorable prognosis in patients with major or complete response, radical surgery might represent overtreatment. OBJECTIVE: This study aimed to evaluate postoperative short-term morbidity, functional outcome, and oncologic long-term outcome in patients with rectal cancer treated with local excision by transanal endoscopic microsurgery or radical surgery and to determine who achieved a complete or major pathological response (ypT0-1) after neoadjuvant treatment. DESIGN: This was a retrospective study. SETTING: The study was conducted at a single center. PATIENTS: Patients who had received neoadjuvant treatment by local excision with a major or complete pathological response at histological examination (transanal endoscopic microsurgery group) were compared to patients treated by radical surgery with the same pathological response (total mesorectal excision group). INTERVENTIONS: The interventions included local excision by transanal endoscopic microsurgery and radical surgery with total mesorectal excision. MAIN OUTCOME MEASURES: Postoperative short-term morbidity, functional outcome 1 year after surgery, and oncologic long-term outcome were measured. RESULTS: Ninety-three patients were included in the study (35 in the transanal endoscopic microsurgery group and 58 in the mesorectal excision group). In the total mesorectal excision group, a sphincter-saving approach was possible in 89.7% (vs 100%; p = 0.049); a protective temporary stoma was necessary in 74.1% of radical procedures (vs 0%; p < 0.001), and 13.8% of these became permanent. Short-term postoperative morbidity was lower after local excision (14.3% vs 46.6%; p = 0.002). One year after surgery, the transanal endoscopic microsurgery group recorded better evacuation and continence function than the total mesorectal excision group. Oncologic outcome was similar between the groups. LIMITATIONS: This study had a retrospective design. CONCLUSION: If a major or complete pathological response occurs after neoadjuvant treatment, an organ-sparing approach by local excision seems to offer the same oncologic results as radical surgery, but it has a better postoperative morbidity rate and better functional results. See Video Abstract at http://links.lww.com/DCR/B901 .Microcirugía endoscópica transanal versus escisión total del mesorrecto en cáncer de recto ypT0-1 después de radioquimioterapia preoperatoria: morbilidad posoperatoria, resultados funcionales y resultado oncológico a largo plazo. ANTECEDENTES: En pacientes con cáncer rectal extraperitoneal localmente avanzado, un abordaje multidisciplinario con radioquimioterapia preoperatoria y cirugía con escisión total del mesorrecto representa el tratamiento estándar. En pacientes que obtienen una respuesta mayor o completa, la cirugía radical puede representar un sobretratamiento, considerando el pronóstico favorable de estos casos. OBJETIVO: Evaluar la morbilidad posoperatoria a corto plazo, el resultado funcional y el resultado oncológico a largo plazo en pacientes con cáncer de recto tratados con escisión local mediante microcirugía endoscópica transanal o mediante cirugía radical y que obtuvieron una respuesta patológica completa o mayor (ypT0-1) después del tratamiento neoadyuvante. DISEO: Este fue un estudio retrospectivo. AJUSTE: El estudio se realizó en un solo centro. ESCENARIO: El estudio se realizó en un solo centro. PACIENTES: Se comparó a los pacientes tratados, tras tratamiento neoadyuvante (1996-2016), mediante escisión local con respuesta patológica mayor o completa al examen histológico (grupo de microcirugía endoscópica transanal), con los pacientes tratados mediante cirugía radical con la misma respuesta patológica (grupo de escisión mesorrectal total). INTERVENCIONES: Extirpación local mediante microcirugía endoscópica transanal y cirugía radical con escisión mesorrectal total. PRINCIPALES MEDIDAS DE RESULTADO: Morbilidad posoperatoria a corto plazo, resultado funcional a un año después de la cirugía (evaluado con una puntuación de evacuación y continencia) y resultado oncológico a largo plazo. LIMITACIONES: Las limitaciones de este estudio incluyen su diseño retrospectivo. CONCLUSIN: Si se produce una respuesta patológica mayor o completa después del tratamiento neoadyuvante, un abordaje con preservación de órganos mediante escisión local parece ofrecer los mismos resultados oncológicos que la cirugía radical, pero tiene una menor tasa de morbilidad postoperatoria y mejores resultados funcionales un año después de la cirugía. Consulte Video Resumen en http://links.lww.com/DCR/B901 . (Traducción-Dr. Felipe Bellolio ).

Risk factors for anastomotic leakage after anterior resection for rectal cancer (RALAR study): A nationwide retrospective study of the Italian Society of Surgical Oncology Colorectal Cancer Network Collaborative Group.

AIM: Anastomotic leakage after restorative surgery for rectal cancer shows high morbidity and related mortality. Identification of risk factors could change operative planning, with indications for stoma construction. This retrospective multicentre study aims to assess the anastomotic leak rate, identify the independent risk factors and develop a clinical prediction model to calculate the probability of leakage. METHODS: The study used data from 24 Italian referral centres of the Colorectal Cancer Network of the Italian Society of Surgical Oncology. Patients were classified into two groups, AL (anastomotic leak) or NoAL (no anastomotic leak). The effect of patient-, disease-, treatment- and postoperative outcome-related factors on anastomotic leak after univariable and multivariable analysis was measured. RESULTS: A total of 5398 patients were included, 552 in group AL and 4846 in group NoAL. The overall incidence of leaks was 10.2%, with a mean time interval of 6.8 days. The 30-day leak-related mortality was 2.6%. Sex, body mass index, tumour location, type of approach, number of cartridges employed, weight loss, clinical T stage and combined multiorgan resection were identified as independent risk factors. The stoma did not reduce the leak rate but significantly decreased leak severity and reoperation rate. A nomogram with a risk score (RALAR score) was developed to predict anastomotic leak risk at the end of resection. CONCLUSIONS: While a defunctioning stoma did not affect the leak risk, it significantly reduced its severity. Surgeons should recognize independent risk factors for leaks at the end of rectal resection and could calculate a risk score to select high-risk patients eligible for protective stoma construction.

Long-Term Outcomes of Local Excision Following Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.

BACKGROUND: Local excision might represent an alternative to total mesorectal excision for patients with locally advanced rectal cancer who achieve a major or complete clinical response after neoadjuvant chemoradiotherapy. METHODS: Between August 2005 and July 2011, 63 patients with mid-low rectal adenocarcinoma who had a major/complete clinical response after neoadjuvant chemoradiotherapy were enrolled in a multicenter prospective phase 2 trial and underwent transanal full thickness local excision. The main endpoint of this study was to evaluate the 5- and 10-year overall, relapse-free, local, and distant relapse-free survival, which were calculated by applying the Kaplan-Meier method. The rate of patients with rectum preserved and without stoma were also calculated. RESULTS: Of 63 patients, 38 (60%) were male and 25 (40%) were female, with a median (range) age of 64 (25-82) years. At baseline, the following clinical stages were found: cT2, n = 21 (33.3%); cT3, n = 42 (66.6%), 39 (61.9%) patients were cN+. At a median (range) follow-up of 108 (32-166) months, the estimated cumulative 5- and 10-year overall survival, relapse-free survival, local recurrence-free survival, and distant recurrence-free survival were 87% (95% CI 76-93) and 79% (95% CI 66-87), 89% (95% CI 78-94) and 82% (95% CI 66-91), both 91% (95% CI 81-96), and 90% (95% CI 80-95) and 86% (95% CI 73-93), respectively. Overall, 49 (77.8%) patients had their rectum preserved, and 54 (84.1%) were stoma-free. CONCLUSION: In highly selected patients, the local excision approach after neoadjuvant chemoradiotherapy is associated with excellent long-term outcomes, high rates of rectum preservation and absence of permanent stoma.

Craniosynostosis-microphthalmia syndrome belongs to the spectrum of BCOR-related disorders.

Craniosynostosis-microphthalmia linked to BCOR haploinsufficiency.

Polyvinylidene Fluoride Mesh (PVDF, DynaMesh®-IPOM) in The Laparoscopic Treatment of Incisional Hernia: A Prospective Comparative Trial versus Gore® ePTFE DUALMESH® Plus.

BACKGROUND: Laparoscopic approach is now generally accepted for the treatment of incisional hernia. The ideal mesh is still to be found. The aim of this study is to compare the well-known Gore® DUALMESH® Plus (WL Gore & Associates, Flagstaff, AZ) to a new prosthesis, the DynaMesh®-IPOM (FEG Textiltechnik GmbH, Aachen, Germany), to clinically verify its potential benefits in the laparoscopic treatment of incisional hernia. MATERIALS AND METHODS: Comparing the results of the laparoscopic treatment of two groups of patients affected by incisional hernia using Gore® DUALMESH® Plus and DynaMesh®-IPOM. RESULTS: There were 45 females and 31 males, with age variable from 21 to 84 years of age. The two groups were well matched for age (median age 60 years for group A and 57.6 years for group B-p=0.44) and sex (28F and 17M group A and 13 F and 18 M group B-p=0.008), while median BMI resulted slightly higher in group B (26.12 group A and 29.74 group B-p=0.001). The median size of the defect was similar in the two groups (87.5 mm group A and 83.4 mm for group B-p=0.83), while the median operating time was slightly longer in group A (77 min group A and 67 min group B-p=0.44). No difference in the length of hospital stay was evidenced between the two groups (3.19 days for group A and 3 days for group B-p=0.74). Time to return to physical activity was similar between the two groups (13.46 days for group A and 12.7 days for group B-p=0.32). Minor complications occurred in 15 cases (19.7%): seromas (7 cases), prolonged ileus (6 cases), and hemoperitoneum (2 cases), without significant difference in the incidence of such complications in the two groups. Five recurrences (6.5% of cases) occurred. No differences in the recurrence rate was noted between the two groups (3 cases/7% for group A and 2 cases/6% for group B-p=00.7). CONCLUSIONS: DynaMesh®-IPOM proved to be a safe and effective mesh for the laparoscopic repair of incisional hernia even when compared to DUALMESH® Plus.

The predictive value of 18F-FDG PET/CT for assessing pathological response and survival in locally advanced rectal cancer after neoadjuvant radiochemotherapy.

PURPOSE: To evaluate whether metabolic changes in the primary tumour during and after preoperative radiochemotherapy (RCT) can predict the histopathological response in patients with locally advanced rectal cancer as well as disease-free survival (DFS) and overall survival (OS). METHODS: Consecutive patients with cT2-4 N0-2 rectal adenocarcinoma were included. (18)F-FDG PET/CT was performed at baseline, at the end of the second week of RCT (early PET/CT) and before surgery (late PET/CT). The PET/CT results were compared with histopathological data (ypT0 N0 vs. ypT1-4 N0-2 as well as TRG1 vs.TRG2-5) and survival. RESULTS: The study included 126 patients. Among 124 patients in whom TNM classification was available, 28 (22.6 %) were ypT0 N0, and among all 126 patients, 31 (24.6 %) were TRG1. The areas under the curve of the early response index (RI) for identifying non-complete pathological response (non-cPR) were 0.74 (95 % CI 0.61 - 0.87) for ypT1-4 N0-2 patients and 0.75 (95 % CI 0.62 - 0.88) for TRG2-5 patients. The optimal cut-off for differentiating patients with non-cPR and cPR was found to be a reduction of 61.2 % (83.1 % sensitivity and 65 % specificity in ypT1-4 N0-2 patients; 85.4 % sensitivity and 65.2 % specificity in TRG2-5 patients). The optimal cut-off for late RI could not be found. The qualitative analysis of images obtained after RCT demonstrated 81.5 % sensitivity and 61.3 % specificity in predicting TRG2-5. After a median follow-up of 68 months, the low number of patients with local/distant recurrence or who had died did not allow the value of PET/CT for predicting DFS and OS to be calculated. CONCLUSION: The early assessment of response to RCT by (18)F-FDG PET/CT can predict non-cPR allowing practical modification of preoperative treatment. Conversely, late RI is not sufficiently accurate for guiding the decision as to whether local excision or even observation is appropriate in an individual patient. Qualitative analysis of late PET/CT images is also not sensitive enough alone to rule out the presence of residual disease.

Risk factors for wound complications in patients undergoing primary closure of the perineal defect after total proctectomy.

PURPOSE: Perineal wounds after complete proctectomy are at risk for failure, with dramatic consequences on patients' health and quality of life. This study is aimed at identifying risk factors for wound complications in patients undergoing primary closure of the perineal defect after total proctectomy. METHODS: Data from 284 patients undergoing total proctectomy from 2002 to 2012 either at the University of Chicago Medical Center or the Catholic University of Rome Hospital were collected and analyzed. RESULTS: Overall, the perineal wound complication rate was 21.8%. Successful conservative management was accomplished in 45.2% of cases. Complications occurred significantly more often in patients with a higher Charlson score index, with the diagnosis of rectal cancer, who had received preoperative radiation and who had a surgical drain placed at the time of initial surgery. Neoadjuvant radiation was the only significant risk factor at multivariate analysis (OR 4.40). In the rectal cancer subgroup, younger age, female gender, and preoperative radiation were predictors of wound complications. Based on that, a 3-point score (radiation, age, and gender (RAG)) was developed. Patients with a score of 3 had a 50% risk of developing a perineal wound complication. CONCLUSIONS: Perineal wound complications are a common and burdensome problem after total proctectomy. Preoperative radiation is the single most significant and controllable risk factor predicting perineal wound failure. In the presence of multiple, non-modifiable risk factors, alternative approaches to primary closure should be considered in managing complex perineal defects.

Rectal sparing approach after preoperative radio - and/or Chemo-therapy (ReSARCh): a prospective, multicentre, observational study.

BACKGROUND: Rectal-sparing approaches for patients with rectal cancer who achieved a complete or major response following neoadjuvant therapy constitute a paradigm of a potential shift in the management of patients with rectal cancer, however their role remains controversial. The aim of this study was to investigate the feasibility of rectal-sparing approaches to preserve the rectum without impairing the outcomes. METHODS: This prospective, multicentre, observational study investigated the outcomes of patients with clinical stage II-III mid-low rectal adenocarcinoma treated with any neoadjuvant therapy, and either transanal local excision or watch-and-wait approach, based on tumor response (major or complete) and patient/surgeon choice. The primary endpoint of the study was rectum preservation at a minimum follow-up of two years. Secondary endpoints were overall, disease-free, local and distant recurrence-free, and stoma-free survival at three years. RESULTS: Of 178 patients enrolled in 16 centres, 112 (62.9%) were managed with local excision and 66 (37.1%) with watch-and-wait. At a median (interquartile range) follow-up of 36.1 (30.6-45.6) months, the rectum was preserved in 144 (80.9%) patients. The 3-year rectum-sparing, overall, disease-free, local recurrence-free, distant recurrence-free survival was 80.6% (95%CI 73.9-85.8), 97.6% (95%CI 93.6-99.1), 90.0% (95%CI 84.3-93.7), 94.7% (95%CI 90.1-97.2), and 94.6% (95%CI 89.9-97.2), respectively. The 3-year stoma-free survival was 95.0% (95%CI 89.5-97.6). The 3-year regrowth-free survival in the watch-and-wait group was 71.8% (95%CI 59.9-81.2). CONCLUSIONS: In rectal cancer patients with major or complete clinical response after neoadjuvant therapy, the rectum can be preserved in about 80% of cases, without compromise the outcomes.

Local excision after preoperative chemoradiotherapy for rectal cancer: results of a multicenter phase II clinical trial.

BACKGROUND: Transanal local excision has been suggested as an attractive approach for patients with rectal cancer who show a major clinical response after preoperative chemoradiotherapy. OBJECTIVE: To evaluate the impact of transanal local excision on the local recurrence of rectal cancer in patients who had a major clinical response after preoperative chemoradiotherapy. DESIGN: Sequential 2-stage phase II study for early efficacy. SETTING: Multicenter study. PATIENTS: Patients with clinical T3 or low-lying T2 rectal adenocarcinoma that showed a major clinical response after a preoperative chemoradiotherapy. Eligible patients underwent a full-thickness transanal local excision. According to their histopathology, the patients staged as ypT0-1 were observed, while the remaining patients were recommended to undergo a subsequent total mesorectal excision. MAIN OUTCOME MEASURES: A local recurrence rate of ≤5% was set as a successful rate for stopping the trial early after the first stage. RESULTS: The study group included 63 patients. Before chemoradiotherapy, patients were staged as clinical T3 (n = 42) and T2 (n = 21). After the local excision, 43 patients fulfilled the criteria to be observed with no further treatment. Nine of the remaining 20 patients for whom a subsequent total mesorectal excision was recommended refused surgery. Two of these patients who refused surgery had intraluminal local recurrence; both had a ypT2 tumor and underwent salvage surgery. The estimated cumulative 3-year overall survival, disease-free survival and local disease-free survival were 91.5% (95% CI: 75.9-97.2), 91.0% (95% CI: 77.0-96.6) and 96.9% (95% CI: 80.3-99.5), respectively. LIMITATIONS: The time of follow-up is still short and the sample size is limited. CONCLUSIONS: Our data suggest that local excision is a good option for patients with a major clinical response after chemoradiotherapy. A longer period of follow-up is required to confirm these findings.

Role and Morbidity of Protective Ileostomy after Anterior Resection for Rectal Cancer: One Centre Experience and Review of Literature.

The creation of a protective stoma is considered a valid life-saving tool, significantly reducing the effects of anastomotic leakage in terms of related morbidity, mortality, and reoperation rate. The aim of this study was to evaluate the impact of a protective loop ileostomy in terms of short- and long-term postoperative morbidity, quantifying the stoma-related complications arising after stoma creation and stoma closure and the risk of permanent stoma. From January 2009 to January 2020, 149 patients with rectal cancer treated by anterior resection and protective ileostomy were enrolled in the study. A total of 113 (75.84%) patients were preoperatively treated with neoadjuvant radiochemotherapy. A clinically relevant anastomotic leak occurred in two patients (1.34%). The postoperative stoma complication rate was 6%. According to the Clavien classification, the stoma-related complication grade was I in seven patients (4.7%) and II in two patients (1.3%). A late stoma-related parastomal hernia occurred in one patient (0.67%). In 129 patients (86.57%), it was possible to close the stoma. Postoperative complications of stoma closure occurred in 12 patients (9.3%). The stoma closure complication grade was I in seven cases (5.43%), II in two cases (1.55%), and ≥3 in three cases (2.33%). Incisional hernia was the only late complication recorded in seven cases (5.42%). The permanent stoma rate was 13.43%. A protective ileostomy has a nonnegligible complication rate, but the rate of severe complications is low. Every effort should be made to clearly identify patients in whom the risk of anastomotic leakage justifies the stoma.

Effectiveness and Validation of the Italian Translation of the Low Anterior Resection Syndrome Score in an Italian High-Volume University Hospital.

Background: The low anterior resection syndrome (LARS) score is a validated questionnaire developed in Denmark to measure the severity of bowel dysfunction after low anterior resection. This retrospective study aimed to assess the effectiveness of the LARS score in the Italian language in a population of Italian patients who underwent low anterior resection for rectal cancer. The convergent and discriminative validity and the test-retest reliability of the score were investigated. Methods: A cohort of two hundred and five patients treated with low anterior resection were enrolled in an Italian high-volume university hospital between January 2000 and April 2018. The Italian version of the LARS score (tested twice), as translated from English original version, a single question on quality of life and the EORTC QLQ-C30 questionnaire were submitted to patients. Results: A high proportion of patients showed a perfect or moderate fit between the LARS score and QoL categories (convergent validity, p < 0.0005). All differences regarding the items of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC QLQ-C30) functional scales were statistically significant (p < 0.0005). The LARS score was able to discriminate between groups of patients who received or did not receive preoperative chemoradiotherapy (p < 0.0005) and those who received total or partial mesorectal excision (p < 0.0005). The test-retest reliability was excellent (intraclass correlation coefficient 0.96). Conclusion: The Italian translation of the LARS score is an easy and reliable tool for assessing bowel dysfunction after low anterior resection and its routine use in clinical practice should be recommended.Trial registration number at www.clinicaltrials.gov: NCT04406311.

The Role of Simultaneous Integrated Boost in Locally Advanced Rectal Cancer Patients with Positive Lateral Pelvic Lymph Nodes.

Aims: Between 11 to 14% of patients with locally advanced rectal cancer (LARC) have positive lateral pelvic lymph nodes (LPLN) at diagnosis, related to a worse prognosis with a 5-year survival rate between 30 to 40%. The best treatment choice for this group of patients is still a challenge. The optimal radiotherapy (RT) dose for LPLN patients has been investigated. Methods: We retrospectively collected data from LARC patients with LPLN at the primary staging MRI, treated in our center from March 2003 to December 2020. Patients underwent a neoadjuvant concomitant chemo-radiotherapy (CRT) treatment on the primary tumor (T), mesorectum, and pelvic nodes, associated with a fluoride-based chemotherapy. The total reached dose was 45 Gy at 1.8 Gy/fr on the elective sites and 55 Gy at 2.2 Gy/fr on the disease and mesorectum. Patients were divided in two groups based on whether they received a simultaneous integrated RT boost on the LPLN or not. Overall Survival (OS), Disease Free Survival (DFS), Metastasis Free Survival (MFS), and Local Control (LC) were evaluated in the whole group and then compared between the two groups. Results: A total of 176 patients were evaluated: 82 were included in the RT boost group and 94 in the non-RT boost group. The median follow-up period was 57.8 months. All the clinical endpoint (OS, DFS, MFS, LC), resulted were affected by the simultaneous integrated boost on LPLN with a survival rate of 84.7%, 79.5%, 84.1%, and 92%, respectively, in the entire population. From the comparison of the two groups, there was a statistical significance towards the RT boost group with a p < 0.006, 0.030, 0.042, 0.026, respectively. Conclusions: Concomitant radiotherapy boost on positive LPLN has shown to be beneficial on the survival outcomes (OS, DFS, MFR, and LC) in patients with LARC and LPLN. This analysis demonstrates that a higher dose of radiotherapy on positive pelvic lymph nodes led not only to a higher local control but also to a better survival rate. These results, if validated by future prospective studies, can bring a valid alternative to the surgery dissection without the important side effects and permanent disabilities observed during the years.

BRIDGE -1 TRIAL: BReak Interval Delayed surgery for Gastrointestinal Extraperitoneal rectal cancer, a multicentric phase III randomized trial.

Design: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC).Several studies have shown a correlation between a longer interval between the end of nCRT and surgery (surgical interval - SI) and an increased pathological complete response (pCR) rate, with a maximum obtained between 10 and 13 weeks.The primary endpoint of this multicenter, 2-arm randomised trial is to investigate SI lengthening, evaluating the difference in terms of complete response (CR) and Tumor Regression Grade (TRG)1 rate in the two arms. Secondly, the impact of SI lengthening on survival outcomes and quality of life (QoL) will be investigated. Methods: Intermediate-risk LARC patients undergoing nCRT will be prospectively included in the study. nCRT will be administered with a total dose of 55 Gy in 25 fractions on Gross Tumor Volume (GTV) plus the corresponding mesorectum of 45 Gy in 25 fractions on the whole pelvis. Chemotherapy with oral capecitabine will be administered continuously.The patients achieving a clinical major or complete response assessed at clinical-instrumental re-evaluation at 7-8 weeks after treatment completion, will be randomized into two groups, to undergo surgery or local excision at 9-11 weeks (control arm) or at 13-16 weeks (experimental arm). Pathological response will be assessed on the surgical specimen using the AJCC TNM v.7 and the TRG according to Mandard. Patients will be followed up to evaluate toxicity and QoL.The promoter center of the trial will conduct the randomization process through an automated procedure to prevent any possible bias.For sample size calculation, using CR difference of 20% as endpoint, 74 patients per arm will be enrolled. Conclusions: The results of this study may prospectively provide a new time frame for the clinical re-evaluation for complete/major responders patients in order to increase the CR rate to nCRT.Trial registration:ClinicalTrials.gov Identifier: NCT03581344.